Mouse epidermal cell cultures and epidermal cell lines are utilized as models for studying mechanisms of epithelial carcinogenesis in vitro. Low extracellular Ca ions concentration in culture medium selects for proliferating cells while elevated Ca ions induces terminal differentiation. Carcinogen exposure results in the development of cell colonies which are resistant to Ca ions induced terminal differentiation. Tumor promoters, ultraviolet light and chemical agents which produce DNA breaks induce ornithine decarboxylase in epidermal cells. Retinoids inhibit tumor promoter induced ornithine decarboxylase prior to activation of enzyme transcription while corticosteroids, local anesthetics and protease inhibitors, act at a site subsequent to gene activation. Tumor promoters also induce epidermal transglutaminase. Antibodies to adducts resulting from covalent binding of the carcinogens acetylaminofluorene and benzo(a)-pyrene to DNA have provided sensitive (less than 1 picomole) and specific immunoassays to quantitate these binding products in cells and tissues. Such assays can detect quantitative or qualitative alterations in binding in different cell types or under differing exposure conditions.